Wound Healing

PHASES OF WOUND HEALING

• Normal wound healing follows a predictable
pattern that can be divided into overlapping
phases defined by characteristic cellular
populations and biochemical activities:
(a) hemostasis and inflammation,
(b) proliferation, and
(c) maturation and remodeling.
• All wounds need to progress through this series
of cellular and biochemical events that
characterizes the phases of healing in order to
successfully re-establish tissue integrity
• Hemostasis precedes and initiates inflammation
with the ensuing release of chemotactic factors
from the wound site.
• Wounding by definition disrupts tissue integrity,
leading to division of blood vessels and direct
exposure of extracellular matrix to platelets.
• Exposure of subendothelial collagen to platelets
results in platelet aggregation, degranulation, and
activation of the coagulation cascade.
• Platelet α granules release a number of wound-
active substances, such as platelet-derived
growth factor (PDGF), transforming growth
factor-β (TGF-β), platelet activating factor (PAF),
fibronectin, and serotonin.
• In addition to achieving hemostasis, the fibrin
clot serves as scaffolding for the migration into
the wound of inflammatory cells such as
polymorphonuclear leukocytes (PMNs,
neutrophils) and monocytes.
• PMNs are the first infiltrating cells to enter the
wound site, peaking at 24 to 48 hours.
• Increased vascular permeability, local
prostaglandin release, and the presence of
chemotactic substances such as complement
factors,
– interleukin-1 (IL-1),
– tumor necrosis factor-α (TNF-α),
– TGF-β,
– platelet factor 4, or bacterial products all stimulate
neutrophil migration.
• PMNs are also a major source of cytokines
early during inflammation, especially TNF-α3
which may have a significant influence on
subsequent angiogenesis and collagen
synthesis.
• Also release proteases such as collagenases,
which participate in matrix and ground
substance degradation in the early phase of
wound healing.
• The second population of inflammatory cells
that invades the wound consists of
macrophages, which are recognized as being
essential to successful healing.
• 5 Derived from circulating monocytes,
macrophages achieve significant numbers in
the wound by 48 to 96 hours postinjury and
remain present until wound healing is
complete.
• Macrophages, like neutrophils, participate in
wound debridement via phagocytosis and
contribute to microbial stasis via oxygen radical
and nitric oxide synthesis.
• The macrophage’s most pivotal function is
activation and recruitment of other cells via
mediators such as cytokines and growth factors,
as well as directly by cell-cell interaction and
intercellular adhesion molecules (ICAM).
• T lymphocytes comprise another population
of inflammatory/immune cells that routinely
invades the wound.
• T-lymphocyte numbers peak at about 1 week
postinjury and truly bridge the transition from
the inflammatory to the proliferative phase of
healing.
• Lymphocytes also exert a downregulating
effect on fibroblast collagen synthesis by cell-
associated interferon (IFN)-γ, TNF-α, and IL-1.
• This effect is lost if the cells are physically
separated, suggesting that extracellular matrix
synthesis is regulated not only via soluble
factors but also by direct cell-cell contact
between lymphocytes and fibroblasts.
 Proliferation
• The proliferative phase is the second phase of wound
healing and roughly spans days 4 through 12.
• It is during this phase that tissue continuity is re-
established. Fibroblasts and endothelial cells are the last
cell populations to infiltrate the healing wound, and the
strongest chemotactic factor for fibroblasts is PDGF.
• Upon entering the wound environment,recruited
fibroblasts first need to proliferate, and then become
activated, to carry out their primary function of matrix
synthesis remodeling. This activation is mediated mainly by
the cytokines and growth factors released from wound
macrophages.
• Fibroblasts isolated from wounds synthesize
more collagen than nonwound fibroblasts, they
proliferate less, and they actively carry out matrix
contraction
• Endothelial cells also proliferate extensively
during this phase of healing. These cells
participate in the formation of new capillaries
(angiogenesis), a process essential to successful
wound healing. Endothelial cells migrate from
intact venules close to the wound. Their
migration, replication, and new capillary tubule
formation is under the influence of such
cytokines and growth factors as TNF-α, TGF-β,
and VEGF.
 Matrix Synthesis
• Biochemistry of Collagen
• Collagen, the most abundant protein in the body,
plays a critical role in the successful completion
of adult wound healing. Its deposition,
maturation, and subsequent remodeling are
essential to the functional integrity of the wound.
Although there are at least 18 types of collagen
described, the main ones of interest to wound
repair are types I and III. Type I collagen is the
major component of extracellular matrix in skin.
• Collagen synthesis, as well as posttranslational
modifications, are highly dependent on
systemic factors such as an adequate oxygen
supply; the presence of sufficient nutrients
(amino acids and carbohydrates) and cofactors
(vitamins and trace metals); and the local
wound environment (vascular supply and lack
of infection).
• Proteoglycan Synthesis
• Glycosaminoglycans comprise a large portion
of the “ground substance” that makes up
granulation tissue. Rarely found free, they
couple with proteins to form proteoglycans.
The polysaccharide chain is made up of
repeating disaccharide units composed of
glucuronic or iduronic acid and a hexosamine,
which is usually sulfated.
• The major glycosaminoglycans present in
wounds are dermatan and chondroitin sulfate.
Fibroblasts synthesize these compounds,
increasing their concentration greatly during
the first 3 weeks of healing.
• As scar collagen is deposited, the
proteoglycans are incorporated into the
collagen scaffolding. However, with scar
maturation and collagen remodeling, the
content of proteoglycans gradually diminishes
TREATMENT OF WOUNDS
 Local Care
• Management of acute wounds begins with
obtaining a careful history of the events
surrounding the injury. The history is followed
by a meticulous examination of the wound.
• Examination should assess the depth and
configuration of the wound, the extent of
nonviable tissue, and the presence of foreign
bodies and other contaminants.
• Examination of the wound may require
irrigation and débridement of the edges of the
wound and is facilitated by use of local
anesthesia.
• Antibiotic administration and tetanus
prophylaxis may be needed, and planning the
type and timing of wound repair should take
place
1.
Management of acute wound
Examination
a. depth? Underlying
structures injury 3. Approximation
b. Configuration? a. Deep layers
c. Nonviable tissue? a. Fascial layers only
b. Absorbable suture
b. Superficial layers
a. Meticulous alignment
b. Nonabsorbable
sutures in skin
c. Monofilament
2. Preparation
d. Dermal glues
a. Anasthetic
b. Exploration
c. Cleansing
d. Hemostatis
e. Debride
nonviable tissue
f. Betadine 4. follow-up
g. Antibiotics a. cellulitis/drainage?
h. tetanus b. Suture removal
a. 4-5 days for face
b. 7-10 days other
skin
 Antibiotics
• Antibiotics should be used only when there is an
obvious wound infection. Most wounds are
contaminated or colonized with bacteria.
• The presence of a host response constitutes an
infection and justifies the use of antibiotics. Signs
of infection to look for include erythema,
cellulitis, swelling, and purulent discharge.
• Indiscriminate use of antibiotics should be
avoided to prevent emergence of multidrug-
resistant bacteria.
 Dressing
• The main purpose of wound dressings is to provide the ideal environment
for wound healing. The dressing should facilitate the major changes taking
place during healing to produce an optimally healed wound. Although the
ideal dressing still is not a clinical reality, technological advances are
promising.
• Dressings can be classified as primary or secondary. A primary dressing is
placed directly on the wound and may provide absorption of fluids and
prevent desiccation, infection, and adhesion of a secondary dressing. A
secondary dressing is one that is placed on the primary dressing for
further protection, absorption, compression, and occlusion. Many types of
dressings exist and are designed to achieve certain clinically desired
endpoints.
• Absorbent Dressings. Accumulation of wound fluid can lead to
maceration and bacterial overgrowth. Ideally, the dressing should
absorb without getting soaked through, as this would permit
bacteria from the outside to enter the wound. The dressing must be
designed to match the exudative properties of the wound and may
include cotton, wool, and sponge.
• Nonadherent Dressings. Nonadherent dressings are impregnated
with paraffin, petroleum jelly, or water-soluble jelly for use as
nonadherent coverage. A secondary dressing must be placed on top
to seal the edges and prevent desiccation and infection.
• Occlusive and Semiocclusive Dressings. Occlusive and
semiocclusive dressings provide a good environment for clean,
minimally exudative wounds. These film dressings are waterproof
and impervious to microbes but permeable to water vapor and
oxygen.
• Hydrophilic and Hydrophobic Dressings. These dressings are
components of a composite dressing. Hydrophilic dressing aids in
absorption, whereas a hydrophobic dressing is waterproof and
prevents absorption.
• Hydrocolloid and Hydrogel Dressings. Hydrocolloid and hydrogel
dressings attempt to combine the benefits of occlusion and
absorbency. Hydrocolloids and hydrogels form complex structures
with water, and fluid absorption occurs with particle swelling, which
aids in atraumatic removal of the dressing. Absorption of exudates
by the hydrocolloid dressing leaves a yellowish-brown gelatinous
mass after dressing removal that can be washed off. Hydrogel is a
cross-linked polymer that has high water content. Hydrogels allow a
high rate of evaporation without compromising wound hydration,
which makes them useful in burn wound treatment.
• Alginates. Alginates are derived from brown
algae and contain long chains of polysaccharides
containing mannuronic and glucuronic acid. The
ratios of these sugars vary with the species of
algae used, as well as the season of harvest.
Processed as the calcium form, alginates turn into
soluble sodium alginate through ion exchange in
the presence of wound exudates. The polymers
gel, swell, and absorb a great deal of fluid.
Alginates are being used when there is skin loss,
in open surgical wounds with medium exudation,
and on full-thickness chronic wounds.
• Absorbable Materials. Absorbable materials are
mainly used within wounds as hemostats and
include collagen, gelatin, oxidized cellulose, and
oxidized regenerated cellulose.
• Medicated Dressings. Medicated dressings have
long been used as a drug-delivery system. Agents
delivered in the dressings include benzoyl
peroxide, zinc oxide, neomycin, and bacitracin-
zinc. These agents have been shown to increase
epithelialization by 28%.
 Skin Replacements
• All wounds require coverage in order to
prevent evaporative losses and infection and
to provide an environment that promotes
healing. Both acute and chronic wounds may
demand use of skin replacement, and several
options are available.
• Conventional Skin Grafts. Skin grafts have long been used to treat
both acute and chronic wounds. Split- (partial-) thickness grafts
consist of the epidermis plus part of the dermis, whereas full-
thickness grafts retain the entire epidermis and dermis. Autologous
grafts (autografts) are transplants from one site on the body to
another; allogeneic grafts (allografts, homografts are transplants
from a living nonidentical donor or cadaver to the host; and
xenogeneic grafts (heterografts) are taken from another species
(e.g., porcine). Split-thickness grafts require less blood supply to
restore skin function. The dermal component of full-thickness grafts
lends mechanical strength and resists wound contraction better,
resulting in improved cosmesis. Allogeneic and xenogeneic grafts
require the availability of tissue, are subject to rejection, and may
contain pathogens.
• Skin Substitutes. Originally devised to
provide coverage of extensive wounds with
limited availability of autografts, skin
substitutes also have gained acceptance as
natural dressings. Manufactured by tissue
engineering, they combine novel
materialswith living cells to provide functional
skin substitutes, providing a bridge between
dressings and skin grafts
• Gene or Cell Therapy. Given the disappointing
results from the application of purified growth
factors onto wounds, the possible therapeutic
potential of gene therapy has been recognized
and studied. Direct access to the open wound
bed, which characterizes almost all chronic
wounds, has facilitated this therapy. Gene
delivery to wounds includes traditional
approaches such as viral vectors and plasmid
delivery or, more recently, electroporation and
microseeding.
 CLASSIFICATION OF WOUNDS
• Wounds are classified as either acute or chronic.
Acute wounds heal in a predictable manner and
time frame.
• An incised wound that is clean and closed by
sutures is said to heal by primary intention.
Often, because of bacterial contamination or
tissue loss, a wound will be left open to heal by
granulation tissue formation and contraction; this
constitutes healing by secondary intention
• Delayed primary closure, or healing by tertiary
intention, represents a combination of the
first two, consisting of the placement of
sutures, allowing the wound to stay open for a
few days, and the subsequent closure of the
sutures
Factors Affecting Wound Healing